Efficacy of second and third lines of treatment in advanced soft tissue sarcomas: a real-world study

Background Soft tissue sarcomas (STSs) are an uncommon and heterogeneous group of tumours. Several drugs and combinations have been used in clinical practice as second-line (2L) and third-line (3L) treatment. The growth modulation index (GMI) has previously been used as an exploratory efficacy endpoint of drug activity and represents an intra-patient comparison. Methods We performed a real-world retrospective study including all patients with advanced STS who had received at least 2 different lines of treatment for advanced disease between 2010 and 2020 at a single institution. The objective was to study the efficacy of both 2L and 3L treatments, analysing the time to progression (TTP) and the GMI (defined as the ratio of TTP between 2 consecutive lines of therapy). Results Eighty-one patients were included. The median TTP after 2L and 3L treatment was 3.16 and 3.06 months, and the median GMI was 0.81 and 0.74, respectively. The regimens most frequently used in both treatments were trabectedin, gemcitabine-dacarbazine, gemcitabine-docetaxel, pazopanib and ifosfamide. The median TTP by each of these regimens was 2.80, 2.23, 2.83, 4.10, and 5.00 months, and the median GMI was 0.78, 0.73, 0.67, 1.08, and 0.94, respectively. In terms of histotype, we highlight the activity (GMI > 1.33) of gemcitabine-dacarbazine in undifferentiated pleomorphic sarcoma (UPS) and in leiomyosarcoma, pazopanib in UPS, and ifosfamide in synovial sarcoma. Conclusions In our cohort, regimens commonly used after first-line STS treatment showed only slight differences in efficacy, although we found significant activity of specific regimens by histotype (AU)

Efficacy of second and third lines of treatment in advanced soft tissue sarcomas: a real-world study.

BACKGROUND: Soft tissue sarcomas (STSs) are an uncommon and heterogeneous group of tumours. Several drugs and combinations have been used in clinical practice as second-line (2L) and third-line (3L) treatment. The growth modulation index (GMI) has previously been used as an exploratory efficacy endpoint of drug activity and represents an intra-patient comparison. METHODS: We performed a real-world retrospective study including all patients with advanced STS who had received at least 2 different lines of treatment for advanced disease between 2010 and 2020 at a single institution. The objective was to study the efficacy of both 2L and 3L treatments, analysing the time to progression (TTP) and the GMI (defined as the ratio of TTP between 2 consecutive lines of therapy). RESULTS: Eighty-one patients were included. The median TTP after 2L and 3L treatment was 3.16 and 3.06 months, and the median GMI was 0.81 and 0.74, respectively. The regimens most frequently used in both treatments were trabectedin, gemcitabine-dacarbazine, gemcitabine-docetaxel, pazopanib and ifosfamide. The median TTP by each of these regimens was 2.80, 2.23, 2.83, 4.10, and 5.00 months, and the median GMI was 0.78, 0.73, 0.67, 1.08, and 0.94, respectively. In terms of histotype, we highlight the activity (GMI > 1.33) of gemcitabine-dacarbazine in undifferentiated pleomorphic sarcoma (UPS) and in leiomyosarcoma, pazopanib in UPS, and ifosfamide in synovial sarcoma. CONCLUSIONS: In our cohort, regimens commonly used after first-line STS treatment showed only slight differences in efficacy, although we found significant activity of specific regimens by histotype.

The Relationship between the Expression of GATA4 and GATA6 with the Clinical Characteristics and Prognosis of Resectable Pancreatic Adenocarcinoma.

GATA4 and GATA6 are transcription factors involved in the differentiation and development of PDAC. GATA6 expression is related to the classic molecular subtype, while its absence is related to the basal-like molecular subtype. The aim was to determine the clinical utility of IHC determination of GATA4 and GATA6 in a series of patients with resected PDAC. GATA4 and GATA6 expression was studied by IHC in TMA samples of normal tissue, PanIN, tumor tissue and lymph node metastases from a series of 89 patients with resected PDAC. Its relationship with clinicopathologic variables and the outcome was investigated. Seventy-two (81%) tumors were GATA6+ and 37 (42%) were GATA4+. While GATA4 expression was reduced during tumor progression, GATA6 expression remained highly conserved, except in lymph node metastases. All patients with early stages and well-differentiated tumors were GATA6+. The absence of GATA4 expression was related to smoking. Patients with GATA4+ or GATA6+ tumors had significantly lower Ca 19.9 levels. The expression of GATA4 and GATA6 was related to DFS, being more favorable in the GATA4+/GATA6+ group. The determination of the expression of GATA4 and GATA6 by IHC is feasible and provides complementary clinical and prognostic information that can help improve the stratification of patients with PDAC.

Clinical Score to Predict Recurrence in Patients with Stage II and Stage III Colon Cancer.

Background: The prognosis of patients with stage II and stage III colon cancer is heterogeneous. Clinical and pathological characteristics, such as tumor budding, may help to further refine the recurrence risk. Methods: We included all the patients with localized colon cancer at Hospital Universitario La Paz from October 2016 to October 2021. We built a prognostic score for recurrence in the training cohort based on multivariate cox regression analysis and categorized the patients into two risk groups. Results: A total of 440 patients were included in the training cohort. After a median follow-up of 45 months, 81 (18%) patients had a first tumor recurrence. T4, N2, and high tumor budding remained with a p value <0.05 at the last step of the multivariate cox regression model for time to recurrence (TTR). We assigned 2 points to T4 and 1 point to N2 and high tumor budding. Forty-five percent of the patients were assigned to the low-risk group (score = 0). Compared to the high-risk group (score 1−4), patients in the low-risk group had a significantly longer TTR (hazard ratio for disease recurrence of 0.14 (95%CI: 0.00 to 0.90; p < 0.045)). The results were confirmed in the validation cohort. Conclusions: In our study, we built a simple score to predict tumor recurrence based on T4, N2, and high tumor budding. Patients in the low-risk group, that comprised 44% of the cohort, had an excellent prognosis.

Identification of sSIGLEC5 and sLAG3 as New Relapse Predictors in Lung Cancer.

Lung cancer (LC) continues to be the leading cause of cancer-related deaths in both men and women worldwide. After complete tumour resection, around half of the patients suffer from disease relapse, emphasising the critical need for robust relapse predictors in this disease. In search of such biomarkers, 83 patients with non-microcytic lung cancer and 67 healthy volunteers were studied. Pre-operative levels of sSIGLEC5 along with other soluble immune-checkpoints were measured and correlated with their clinical outcome. Soluble SIGLEC5 (sSIGLEC5) levels were higher in plasma from patients with LC compared with healthy volunteers. Looking into those patients who suffered relapse, sSIGLEC5 and sLAG3 were found to be strong relapse predictors. Following a binary logistic regression model, a sSIGLEC5 + sLAG3 score was established for disease relapse prediction (area under the curve 0.8803, 95% confidence intervals 0.7955−0.9652, cut-off > 2.782) in these patients. Based on score cut-off, a Kaplan−Meier analysis showed that patients with high sSIGLEC5 + sLAG3 score had significantly shorter relapse-free survival (p ≤ 0.0001) than those with low sSIGLEC5 + sLAG3 score.Our study suggests that pre-operative sSIGLEC5 + sLAG3 score is a robust relapse predictor in LC patients.

Atypical course of long-term colon cancer.

BACKGROUND: Thyroid metastases are extremely rare, with an incidence of 1-3% according to different data. Colon cancer is the second most common tumor that metastasizes to this organ. CASE REPORT: We report a case of a long-standing colon cancer with an atypical metastatic pattern and the appearance of a thyroid metastases. In addition, we highlight the importance of multidisciplinary management of this pathology and the emerging need to establish next generation sequencing panels for better molecular characterization.

ANTECEDENTES: Las metástasis tiroideas son tremendamente infrecuentes, situándose su incidencia en torno al 1-3% según los diferentes datos. El cáncer de colon es el segundo tumor que con más frecuencia produce metástasis en este órgano. CASO CLÍNICO: Se expone un caso de cáncer de colon de larga evolución con patrón metastásico atípico y aparición de metástasis tiroidea. Además, se señala la importancia del manejo multidisciplinario de esta patología y la necesidad emergente de establecer paneles de secuenciación masiva para una mejor caracterización molecular.

Clinical and therapeutic management of a pleural fibrous tumor with ALK translocation.

We present a clinical case of a solitary fibrous pleural tumor (TFSP) with abnormal behavior due to its high aggressiveness and poor short-term prognosis, where an ALK translocation was identified. TFSP is an infrequent tumor, with an estimated incidence of around 8 per 100,000 inhabitants and with few cases reported in the literature. The most common is that it is a neoplasm of benign behavior, with debut as a localized mass and whose The treatment of choice is surgical resection. All the data in the literature contrast with our experience, which we report below.

Presentamos un caso clínico de un tumor fibroso solitario pleural (TFSP) de comportamiento anómalo por su alta agresividad y mal pronóstico a corto plazo, en el que se identificó una translocación de ALK. El TFSP es un tumor infrecuente, con una incidencia estimada en torno a 8 casos por 100,000 habitantes y con pocos reportes en la literatura. Lo más habitual es que se trate de una neoplasia de comportamiento benigno, con debut como una masa localizada y cuyo tratamiento de elección es la resección quirúrgica. Todos los datos de la literatura contrastan con nuestra experiencia, que presentamos a continuación.

Neoadjuvant Chemoimmunotherapy in Patients with Resectable Non-small Cell Lung Cancer.

OPINION STATEMENT: Worldwide, lung cancer is the most common cause of cancer morbidity and mortality. Despite a trend towards an escalating diagnosis of resectable non-small cell lung cancer (NSCLC), overall survival (OS) in patients with resectable NSCLC remains poor. The incorporation of chemotherapy into the neoadjuvant setting has improved disease-free survival (DFS), time to distant recurrence, and OS. Furthermore, the incorporation of immunotherapy and the combination of chemotherapy and immunotherapy have improved pathological responses, which seems to be associated with increased survival. Therefore, immunotherapy represents a paradigm shift in treating resectable NSCLC. However, validation in large randomized trials is mandatory and a longer postoperative follow-up period is required. Additionally, neoadjuvant therapy trials offer an exceptional environment for testing predictive biomarkers. PD-L1 expression and tumor mutational burden (TMB) are the most helpful tools for predicting the likelihood of response with immunotherapy in metastatic NSCLC. However, in the neoadjuvant setting, PD-L1 expression and TMB have had opposite results until now. Recently, the immune profiling and some immune-related genes also appear to be involved in the prognosis and response to immunotherapy in NSCLC. Further prospective studies are needed to derive definitive conclusions.

[Pulmonary adenocarcinoma with double mutation EGFR: L858R and G719X]. / Adenocarcinoma de pulmón con doble mutación de EGFR: L858R y G719X.

Lung cancer with EGFR mutation is rare in our country, with an estimated incidence of 7-10%. It is well known that, in this type of disease, specific inhibitors should be used, as they increase patient survival and therefore prognosis. So-called tumour heterogeneity, the possibility of various mutations concurring in the same tumour, is currently being debated. We present a case of a double mutation of EGFR and discuss treatment, management and possible implications.

The management of metastatic GIST: current standard and investigational therapeutics.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. The majority of GISTs harbor gain of function mutations in either KIT or PDGFRα. Determination of the GIST molecular subtype upon diagnosis is important because this information informs therapeutic decisions in both the adjuvant and metastatic setting. The management of GIST was revolutionized by the introduction of imatinib, a KIT inhibitor, which has become the standard first line treatment for metastatic GIST. However, despite a clinical benefit rate of 80%, the majority of patients with GIST experience disease progression after 2-3 years of imatinib therapy. Second and third line options include sunitinib and regorafenib, respectively, and yield low response rates and limited clinical benefit. There have been recent FDA approvals for GIST including ripretinib in the fourth-line setting and avapritinib for PDGFRA exon 18-mutant GIST. This article aims to review the optimal treatment approach for the management of patients with advanced GIST. It examines the standard treatment options available but also explores the novel treatment approaches in the setting of imatinib refractory GIST.